1. Fever in the returning traveller Viviana Elliott Consultant Acute Medicine 2014

2. Aims To provide a practical initial approach to the diagnosis and management of febrile adult returning from abroad.

3. Objectives 1.To be able to understand the importance of the topic 2.To be able to take a direct related history 3.To be able to correlate incubation period with most likely diagnosis 4.To be able to identify diagnosis that you can’t miss 5.To be able to “call a friend” if you are not sure

4. Why do you think it is important?

5. Coventry’s ethnic diversity Ethnic group% Total Population : 300848 persons100% White British78.3% White Other2.2% Indian8% Pakistani2.1% Black Caribbean1.1% Black African0.6% Black Other0.1% Chinese or other ethnic group: Chinese 0.7%

6. World travel Students 2 universities Coventry college Lecturers Elective students: medics, vets Visiting family and relatives Holiday

7. Aetiology of fever after travel to tropics DiagnosisMacLean et al (n=597)Doherty et al (n=195) Malaria3242 Hepatitis63 Respiratory infection* LRTI- Bronchitis and Pneumonia 112.6 Urinary tract infection42.5 Dengue fever26 Enteric fever22 Diarrhoeal illness4.56.5 Epstein-Barr virus20.5 Pharyngitis12 Rickettsia10.5 Amoebic liver abscess10 Tuberculosis12 Meningitis11 Acute HIV0.31 Miscellaneous6.35 Undiagnosed2524.5 ( viral and non specific infect)

8. History Brief Directed Workout timescales Then you can calculate incubation periods and group likely causes Bonus points if you find something on examination

9. “5 W questions” Who? What? Where? When? Why?

10. “5 W questions” Who? What? Where? When? Why?

11. Who? – risk factors Travellers Sub-Saharan –TB –HIV Homosexual –HIV –Viral Hepatitis Heterosexual –Random casual sexual encounters –Sex Tourism e.g. Thailand South Asian? – TB Others- Tattoos,Piercings, Recreational drug use (IVDU, Dysinhibition)

12. “5 W questions” Who? What? Where? When? Why?

13. What? Occupation –Farmer recently died of listeria at UHCW –Sewerage workers and leptospirosis Activities –Ramblers and tick bites eg. Lyme disease Animal contact

14. “5 W questions” Who? What? Where? When? Why?

15. Details of travel –Malaria endemic country? –Sub-Saharan Africa –TB –Malaria –HIV –South Asian –TB –HIV –Malaria –East Asia –Swine Flu or Bird flu –HIV –Eastern Europe –MDRTB XDRTB –www.cdc.gov Where?

16. “5 W questions” Who? What? Where? When? Why?

17. When? When did they go? When did they return? When did the symptoms start?

18. Incubation period Short (<10 days) Medium (10-21 days) Long (>21 days)

19. Short (<10 days) –Gastroenteritis –Respiratory infection -LRTI- Bronchitis and Pneumonia –Urinary tract infections Common things first!

20. Medium 10-21 days Malaria Enteric fever

21. Long (>21 days) Viral hepatitis Malaria TB HIV

22. “5 W questions” Who? What? Where? When? Why?

23. Why? (travellers) Did they go for sex? Whom did they have sex with? Package holiday? –Low risk

24. Key diagnoses not to miss Malaria Enteric fever HIV TB Because if missed they can result in… –Death –Chronic disability

25. Malaria Originated probably form animal Malaria in central Africa Spread around the world by human migration 500 million people infected every year Holoendemic (most people infected) Sub-saharan Africa > 75 % rate Transmission all year round 75% of the deaths are in children under 5 Adults significant immunity low parasitemia few symptoms

26. World-wide distribution

27. Malaria in the UK Imported into the UK from tropical countries 1500-2000 cases reported each year 10-20 deaths

28. Human Malaria – 4 species ¾ reported malaria cases in the UK are caused by Plasmodium falciparum, which can lead to life threatening multi-organ disease. Most non-falciparum malaria cases are caused by Plasmodium vivax Few cases are caused by Plasmodium ovale or Plasmodium malariae.

30. Clinical presentation In non-immune individuals(children in any area, adults in hypoendemica area (0-10 % rate) and visitors to non- malarious region Incubation 10-21 days (longer) Symptoms: Malaise Fever (up to 41˚ C) Rigors Drenching sweats Vomiting or diarrhoea

31. P. vivax or P. ovale infection Mild illness Gradual anaemia May be tender hepatomegaly Recovery 2-4 weeks Hypnozoites in liver can cause relapses for many years after infection Chronic ill health due to anaemia and hyperactive splenomegaly

32. P. malariae infection Mild illness but tends to run a more chronic course In children can cause Glonerulonephritis and nephrotic syndrome

33. P. falciparium Vast majority of malaria death are due to P. Falciparum Patients deteriorate rapidly Higher risk of bacterial infections “Blackwater fever” is due to widespread intravascular haemolysis affecting parasitized and unparasitized red cell giving rise to dark urine

34. How do we diagnose malaria?

35. Specific and urgent investigation “Malaria parasites” Thick (find it) Thin (typify it) Rapid antigen test Less sensitive for non falciparum No info about parasite count, maturity or mixed species Use in adjunct with microscopy

36. Why high risk of hypoglycaemia in P falciparum malaria ?

37. Review Malaria algorithm

38. Why high risk of hypoglycaemia? Plasmodium use of glucose 75% greater than normal red cell Quinine and Quinidine stimulates secretion of insuline Associated to cerebral malaria > children and pregnant woman

39. Key features Malaria Malaria is a medical emergency and patients withsuspected malaria should be evaluated immediately Return travellers with fever and any other symptoms Geographical distribution ( beware of package holidays to the Gambia) Think of relapse in the absence of recent travel

40. Enteric Fever 16 million new cases worldwide mainly India and Africa 600.000death per year Typhoid is caused by Salmonella typhi Typical form of Enteric Fever Paratyphoid is caused by Salmonella paratyphy A,B or C Less severe illness

41. Acute systemic illness: Incubation period: 10-14 days Food/water- borne Symptoms: –Headache –Fever –Abdominal discomfort

42. Clinical Presentation of Enteric Fever Fever is almost invariable relative bradycardia only first week

43. Clinical Presentation of Enteric Fever Constipation more common than diarrhoea initial loose stools fairly common Maybe evanescent rash: “Rose spots”

44. Investigations First Week: Bloods: low WBC, platelets and mildly raised LFTs BCM positive 40-80% Second week Urine culture 0-58% Stool culture 35-65% Bone marrowhigher sensitivity than BCM Newer rapid serology IgM against specific S Typhi Widal test lacks sensitivity and specificity not recommended

45. Complications Incidence: 10-15% illness >2 weeks GI Bleed Intestinal perforation Typhoid encephalopathy Vaccination provides incomplete protection

46. Treatment Unstable treat empirically pending BCM First choice: Ceftriaxone 2g iv 70% of isolated S typhi and paratyphi imported into UK are resistant to Ciprofloxacin In patients returning from Africa resistance 4% If resistance to Ciprofloxacin: Azitromycin NOTE: fever take some time to respond regardless of antibiotic use failure to defervesce is not a reason to change antibiotics if sensitive

47. Key features Enteric fever Salmonella typhi Food/water- borne Especially South Asia travel Any traveller with fever and headache returning in the last 21 days Diarrhoea often absent or late in illness Blood culture diagnosis Septicaemia and death

48. Human Immunodeficiency Virus (HIV) 40 million people are HIV + and half of them are in Africa (WHO 2004) HIV 1 (retrovirus) is responsible for most cases world wilde HIV 2 related virus produces similar illness with longer latent period 3 million have acquired immunodeficiency syndrome (AIDS)

49. Transmission Sexual contact 75% Infected blood products IV drug abuse Perinatal

50. Stages of infection Acute infection: asymptomatic Sero-conversion: transient illness 2-6 weeks after HIV infection: fever, malaise, myalgia, pharyngitis, maculopapular rash or meningngoencephalitis (rare) Persistent generalised lymphadenopathy (PGL) nodes :1 cm and ≥ 2 extra-inguinal sites for 3 months + Opportunistic infections: Candida, herpes zoster, tenia infections (AIDS related complex)

51. Key features HIV –Risk group –Recurrent infections Herpes zoster –Oral candida –Persistent lymphadenopathy –Anaemia, leucopaenia, thrombocytopaenia

52. Key features TB Risk group Chronic systemic and respiratory symptoms Unresolving symptoms, raised inflammatory markers and belonging to a risk group Beware of protean manifestions

53. Key points Think of the 5 Ws Risk factors for disease Don’t miss… –Malaria (knowledge of travel) –Enteric fever (knowledge of travel) –HIV (risk group) – TB (risk group)

55. Useful websites www.britishinfectionsociety.org www.who.int www.hpa.org.uk http://www.istm.org/geosentinel/main.html Further reading : “Fever in the returning traveller part II in website”